Epidermal growth factor receptor signaling pathway involved in progestin‐resistance of human endometrial carcinoma: In a mouse model

Xü, Yanli; Tong, Jianqian; Ai, Zhihong; Wang, Juan; Teng, Yincheng

doi:10.1111/j.1447-0756.2012.01881.x

Cited by 20 publications

(8 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, Wnt signaling pathway, important signaling pathways in the carcinogenesis and embryogenesis, has been implicated in endometrial carcinogenesis [ 35 ]. Previous studies have demonstrated a significant correlation of EGFR overexpression with advanced stage and poor prognosis, suggesting that abnormal activation of EGFR signaling pathway contributes to tumorigenesis and metastasis of UCEC [ 36 ]. Notch signaling pathway is an evolutionally conserved developmental pathway involved in the regulation of cellular proliferation, differentiation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma

Zhou¹,

Zhang²,

Zhao³

et al. 2018

BMC Cancer

View full text Add to dashboard Cite

BackgroundEndometrial cancer (UCEC) is a complex malignant tumor characterized by both genetic level and clinical trial. Patients with UCEC exhibit the similar clinical features, however, they have distinct outcomes due to molecular heterogeneity. The aim of this study was to access the prognostic value of long non-coding RNAs (lncRNAs) in UCEC patients and to identify potential lncRNA signature for predicting patients’ survival and improving patient-tailored treatment.MethodsWe performed a comprehensive genome-wide analysis of lncRNA expression profiles and clinical data in a large cohort of 301 UCEC patients. UCEC patients were randomly divided into the discovery cohort (n = 150) and validation cohort (n = 151). A novel lncRNA-focus expression signature was identified in the discovery cohort, and independently accessed in the validation cohort. Additionally, the lncRNA signature was evaluated by multivariable Cox regression and stratification analysis as well as functional enrichment analysis.ResultsWe detected a novel lncRNA-focus expression signature (LFES) consisting of 11 lncRNAs that were associated with survival based on risk scoring strategy in UCEC. The risk score based on the LFES was able to separate patients of discovery cohort into high-risk and low-risk groups with significantly different overall survival and progression-free survival, and has been successfully confirmed in the validation cohort. Furthermore, the LFES is an independent prognostic predictor of survival and demonstrates superior prognostic performance compared with the clinical covariates for predicting 5-year survival (AUC = 0.887). Functional analysis has linked the expression of prognostic lncRNAs to well-known tumor suppressor or ontogenetic pathways in endometrial carcinogenesis.ConclusionsOur study revealed a novel 11-lncRNA signature to predict survival of UCEC patient. This lncRNA signature may be a valuable and alternative marker for risk evaluation to aid patient-tailored treatment and improve the outcome of patients with UCEC.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3983-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma

Zhou¹,

Zhang²,

Zhao³

et al. 2018

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Down-regulation of progestin receptor (PR) resulting from continuous progestin administration leads to desensitization to progestin [ 13 ], which was thought to be one of the reasons of progestin resistance, while intermittent progestin withdrawal treatment significantly increases the apoptotic rate of endometrial cancer cells [ 14 ]. Other molecules including those in the EGF/EGFR [ 15 , 16 ] and insulin [ 9 ] signaling pathways may also contribute to progestin resistance. In our earlier studies, significant decrease of survivin expression was seen in progestin responders, whereas, no significant level changes of survivin expression were seen in non-responders [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway

Wang

Zhang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Progestin resistance is a main obstacle for endometrial precancer/cancer conservative therapy. Therefore, biomarkers to predict progestin resistance and studies to gain a more detailed understanding of the mechanism are needed. The antioxidant Nrf2-AKR1C1 signal pathway exerts chemopreventive activity. However whether it plays a role in progestin resistance has not been explored. In this study, elevated levels of AKR1C1 and Nrf2 were found in progestin-resistant endometrial epithelia, but not in responsive endometrial glands. Exogenous overexpression of Nrf2/AKR1C1 resulted in progestin resistance. Inversely, silencing of Nrf2 or AKR1C1 rendered endometrial cancer cells more susceptible to progestin treatment. Moreover, medroxyprogesterone acetate withdrawal resulted in suppression of Nrf2/AKR1C1 expression accompanied by a reduction of cellular proliferative activity. In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression. Our findings suggest that overexpression of Nrf2 and AKR1C1 in endometrial precancer/cancer may be part of the molecular mechanisms underlying progestin resistance. If validated in a larger cohort, overexpression of Nrf2 and AKR1C1 may prove to be useful biomarkers to predict progestin resistance. Targeting the Nrf2/AKR1C1 pathway may represent a new therapeutic strategy for treatment of endometrial hyperplasia/cancer.

show abstract

“…In our present research, among the 24384 DEGs, we utilized the top 250 genes to conduct Functional and pathway enrichment analysis and GSEA analysis, which may provide novel insights for clarifying pathogenesis of progestin resistant. As was exhibited in DAVID, the genes were enriched in biological processes (BP) of negative regulation of DNA binding, type I interferon signaling pathway, neuron migration and axonogenesis involved in innervation, which made complementary remarks to previous points that EGF/EGFR [25] and insulin [26] signaling pathways may lead to progestin resistance.…”

Section: Discussionmentioning

confidence: 54%

Screening and identification of MSX1 for predicting progestin resistance in endometrial cancer

Yang

Cui

Huang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Progestin resistance is a critical obstacle for endometrial conservative therapy. Therefore, the studies to acquire a more comprehensive understanding of the mechanisms and specific biomarkers to predict progestin resistance are very important. However, the pivotal roles of essential molecules of progestin resistance are still unexplored.Methods: We downloaded GSE121367 with gene expression profiles of medroxyprogesterone acetate (MPA) resistant and sensitive cell lines from the GEO database. The "limma" R language package was applied to identify differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis was performed through the database of DAVID. Meanwhile, we conducted GSEA analysis to identify pathway enrichments. Protein-protein interaction construction of top genes was conducted to screen hub genes by STRING and visualized in Cytoscape. A high connectivity degree of hub genes were picked out to perform the differential expression, methylation validation and overall survival analysis in the Gene Expression Profiling Interactive Analysis database, Human Protein Atlas database and Kaplan-Meier plotter online tool, respectively. In addition, microRNAs and upstream transcription factors of hub genes were predicted by miRTarBase and Network Analyst database.Results: A total number of 3282 differentially expressed genes were identified. Functional enrichment analysis demonstrated that these genes were mostly enriched in negative regulation of DNA binding, chronic inflammatory response and cell adhesion molecules pathway. We screened out ten hub genes including CDH1, JAG1, PTGES, EPCAM, CNTNAP2, TBX1, MSX1, KRT19, OAS1 and DAB2 among different groups. The genomic alteration rates of hub genes were low based on the current uterine corpus endometrial carcinoma sample sets. Their relevant microRNA and transcription factor were detected and has-miR-335-5p, has-miR-124-3p, MAZ and TFDP1 were the most prominent. The methylation status of CDH1, JAG1, EPCAM and MSX1 were decreased, corresponding to their high protein expression in endometrial cancers, which also indicated better overall survival. The homeobox protein of MSX1 showed significantly tissue specificity.Conclusions: Our study identified ten hub genes associated with progestin resistance of endometrial cancer and screened out the gene of MSX1 which promised to be the specific indicator. This would

show abstract

Epidermal growth factor receptor signaling pathway involved in progestin‐resistance of human endometrial carcinoma: In a mouse model

Abstract: The present study describes an in vivo model that can provide a valuable tool in studying the interaction of overexpressed EGFR and progestin resistance in EC. Gefitinib may be useful in the treatment of progestin-resistant EC.

Cited by 20 publications

References 24 publications

A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma

A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma

Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway

Screening and identification of MSX1 for predicting progestin resistance in endometrial cancer

Contact Info

Product

Resources

About